CK2 inhibition protects white matter from ischemic injury

Selva Baltan, Chinthasagar Bastian, John Quinn, Danielle Aquila, Andrew McCray, Sylvain Brunet

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Strokes occur predominantly in the elderly and white matter (WM) is injured in most strokes, contributing to the disability associated with clinical deficits. Casein kinase 2 (CK2) is expressed in neuronal cells and was reported to be neuroprotective during cerebral ischemia. Recently, we reported that CK2 is abundantly expressed by glial cells and myelin. However, in contrast to its role in cerebral (gray matter) ischemia, CK2 activation during ischemia mediated WM injury via the CDK5 and AKT/GSK3β signaling pathways (Bastian et al., 2018). Subsequently, CK2 inhibition using the small molecule inhibitor CX-4945 correlated with preservation of oligodendrocytes as well as conservation of axon structure and axonal mitochondria, leading to improved functional recovery. Notably, CK2 inhibition promoted WM function when applied before or after ischemic injury by differentially regulating the CDK5 and AKT/GSK3β pathways. Specifically, blockade of the active conformation of AKT conferred post-ischemic protection to young, aging, and old WM, suggesting a common therapeutic target across age groups. CK2 inhibitors are currently being used in clinical trials for cancer patients; therefore, it is important to consider the potential benefits of CK2 inhibitors during an ischemic attack.

Original languageEnglish (US)
Pages (from-to)37-42
Number of pages6
JournalNeuroscience Letters
Volume687
DOIs
StatePublished - Nov 20 2018
Externally publishedYes

Keywords

  • Aging
  • CK2
  • Casein kinase 2
  • Ischemia
  • Protein kinase
  • Signaling
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

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